The heart receives input from the central nervous system in bursts of activity, much of which is synchronized with baroreceptor or respiratory reflexes. The response of the heart to this phasic input varies dependent on the time of arrival of the stimulus during the cardiac cycle. This proposed research is designed to study the phase dependency of parasympathetic simulation on the rate of sinoatrial nodal firing and conduction in the mammalian heart. Preparations of isolated atria and whole animals (rats and/or dogs) will be used in a way to permit stimulation of the heart at precise times. In isolated atria, endogenous neurotransmitters will be released by electrical pulses which are below threshold for activation of myocardial cells. The relationships between cardiac cycle length, time of stimulus delivery, and time of action potential generation in the SA nodal cells themselves will be investigated. Using an analog computer, brief stimuli will be delivered at precise times during the cardiac cycle, and heart rate and time of stimulus delivery will be monitored. In some experiments, SA nodal action potentials will be recorded concurrently with either extracellular electrodes or intracellular microelectrodes. Using whole rats or open-chest dogs, similar experiments will be performed to compare the results found in an isolated rat preparation to those found in whole animals. The nervous system has a profound regulatory effect on the heart. These impulses appear to be clustered in certain phases of the cardiac cycle. If parasympathetic stimulation is delivered at specific times in the cardiac cycle, it causes irregularities. Thus this study on phase-sensitivity to vagal stimulation may have a direct bearig on both normal and pathological (for example: "sick sinus syndrome") control of the heart.